Cognition in Essential Tremor: A Neuroimaging and Biomarker Study

项目摘要/摘要 原发性震颤(ET)是世界上最常见的神经系统疾病之一。除 双侧运动性震颤的显著特征，有特发性震颤的人通常表现为轻度认知 主要被描述为执行困难并被视为与异常有关的变化 在小脑-皮质网络中。然而，越来越多的证据表明，认知障碍可能会扩大。 在额叶-执行领域之外，流行病学研究表明，患有ET的个体在 与年龄匹配的同龄人相比，患痴呆症的风险增加。之前进行的研究由 申请者确定了一组ET患者，他们有更广泛的认知缺陷，包括记忆力差。这 引发了这样一个问题：是否会有更广泛的神经变化发生在 至少一部分ET患者的小脑网络。事实上，神经成像的初步发现 神经病理学研究表明，ET和阿尔茨海默病之间可能存在联系。 有必要进行进一步的研究来探索这种联系，包括检查与认知相关的生物标志物。 拒绝。本研究的总体目标是更好地了解ET中认知的神经关联。 这项拟议的研究旨在1)使用数据驱动(聚类分析)来识别ET中的认知表型 方法和综合神经认知评估，2)确定不同的认知特征在 ET在脑结构上的变化(即游离水、容量)，以及3)探索血浆获得性 与阿尔茨海默病相关的生物标记物在有记忆相关的ET患者中升高 相对于那些不这样做的人来说。拟议研究的创新特点包括确定 患有不同类型认知缺陷的ET患者认知的神经解剖学相关性 应用游离水成像和血浆生物标志物作为早期诊断的灵敏和有效的活体标志物 神经退行性变。这项研究的发现可能会增加目前对自然和 ET认知变化的异质性，有可能提供关于ET之间联系的进一步信息 ET与痴呆症。此外，拟议的项目还将为申请人提供额外的培训。 包括在她的博士课程中。具体地说，培训目标将包括1)磁力方面的实践培训 磁共振成像数据处理和分析，重点是结构成像(T1)和自由水成像，2) 老年性神经病学中神经基础和认知功能障碍机制的课程 障碍，3)与阿尔茨海默病和痴呆症有关的血浆生物标记物的教学，4)培训 使用用于统计计算和神经成像处理的编程语言，5)开发 专业技能和职业技能。申请者有强大的研究环境支持，具有必要的 完成拟议项目所需的资源和基础设施，以及富有成效的指导小组 在拟议的研究领域具有特定的专业知识。

PROJECT SUMMARY/ABSTRACT Essential tremor (ET) is among the most prevalent neurological disorders in the world. In addition to the hallmark feature of bilateral kinetic tremor, individuals with essential tremor often present with mild cognitive changes that have been primarily characterized as dysexecutive and viewed as being related to abnormalities in cerebello-cortical networks. However, growing evidence suggests that cognitive difficulties can extend beyond the frontal-executive domain, and epidemiological research has shown that individuals with ET are at an increased risk for developing dementia compared to age-matched peers. Prior research conducted by the applicant identified a subgroup of ET patients who had broader cognitive deficits, including poor memory. This gives rise to the question of whether there may be more widespread neural changes occurring outside cerebellar networks in at least a subset of individuals with ET. Indeed, preliminary findings from neuroimaging and neuropathological studies have suggested that there may be a link between ET and Alzheimer’s disease. Further research is warranted to explore this link, including examining biomarkers associated with cognitive decline. The overall goal of the current study is to better understand the neural correlates of cognition in ET. The proposed study aims to 1) identify cognitive phenotypes in ET using a data-driven (cluster analytic) approach and comprehensive neurocognitive assessment, 2) determine whether different cognitive profiles in ET vary in structural brain changes (i.e., free-water, volume), and 3) to explore whether plasma-acquired biomarkers associated with Alzheimer’s disease are elevated in individuals with ET who have memory-related changes relative to those who do not. Innovative features of the proposed study include determining neuroanatomical correlates of cognition in individuals with ET who have different types of cognitive deficits and use of free-water imaging and plasma biomarkers as sensitive and powerful in vivo markers of early neurodegeneration. Findings from this study may increase current understanding about the nature and heterogeneity of cognitive changes in ET, with the potential to provide further information on the link between ET and dementia. The proposed project will also provide the applicant with additional training beyond that included in her Ph.D. program. Specifically, training goals will include 1) hands-on training in magnetic resonance imaging data processing and analysis with emphasis on structural (T1) and free-water imaging, 2) coursework in neural bases and mechanisms underlying cognitive dysfunction in age-related neurological disorders, 3) didactics in plasma biomarkers associated with Alzheimer’s disease and dementia, 4) training in using programming languages for statistical computing and neuroimaging processing, 5) development of professional and career skills. The applicant is supported by a strong research environment with the necessary resources and infrastructure for completion of the proposed project, as well as a productive mentoring team with specific expertise in the proposed areas of study.